Tetrabutylammonium Fluoride In THF Research Articles

Synthesis of hybrid materials based on poly(3-hexylthiophen) and modified multiwalled carbon nanotubes

In this study, we reported a new method to synthesize hybrid materials from P3HT and modified MWNTs through SN 2 mechanism using a catalytic system of tetrabutylammonium fluoride in THF (TBAF/THF). Experimental results obtained by scanning electron microscope (SEM), transmission electron microscope (TEM), Raman spectra and sedimentation test confirmed the core-shell structure of the grafted P3HT/MWCNTs. The hybrid material was higher soluble in organic solvents (stable for more than 6 weeks) as well as better thermal stability than P3HT/MWNTs composite.

Novel synthesis of 3,6-disubstituted-1,2,4,5-tetrazine derivatives from hydrazones by using [hydroxyl(tosyloxy)iodo]benzene

Abstract A mild and efficient protocol for the construction of 1,4-dihydro-3,6-disubstituted-1,4-bis( p -toluenesulfonyl)-1,2,4,5-tetrazines from p -toluenesulfonyl hydrazones mediated by [hydroxyl(tosyloxy)iodo]benzene in the presence of pyridine has been developed. This protocol affords the products in good to excellent yields. The corresponding 3,6-disubstituted-1,2,4,5-tetrazines can be easily obtained through one-step N-deprotection of p -toluensulfonyl groups and aromatization by tetrabutyl ammonium fluoride in THF. A mechanism has been proposed.

Synthesis and Study of Oxadisilole‐Fused Benzisoxazoles or Naphthisoxazoles

AbstractOxadisilole‐fused benzisoxazoles or naphthisoxazoles were obtained through 1,3‐dipolar cycloaddition of arynes with nitrile oxides in good yields at room temperature. Key to the procedure is the simultaneous in situ generation of reactive nitrile oxides from arenecarbohydroximoyl chlorides and aryne reactants from benzobis(oxadisilole) or 2,3‐naphthoxadisilole. One oxadisilole‐fused benzisoxazole is a new precursor of a benzyne formed by a phenyliodination/fluoride‐induced elimination protocol. By using this benzyne, cycloadducts were synthesized in good yields. The de‐oxadisilole reaction of some of the oxadisilole‐fused benzisoxazoles could be easily conducted with a 1.0 M solution of tetrabutylammonium fluoride in THF at room temperature.

Synthesis and characterization of novel trifluoromethyl-containing alcohols with Ruppert's reagent

Synthesis and characterization of novel new trifluoromethyl-containing alcohols using Ruppert's reagent [(trimethyl)trifluoromethylsilane] ( 1) are reported. The reactions of 1 with various ketones and aldehydes, such as tetraphenylcyclopentadienone ( 2a), 9,10-anthraquinone ( 2b), pyrenaldehyde ( 2c), 2,6-dimethyl-para-anisaldehyde ( 2d), and 2,3(methylenedioxy)benzaldehyde ( 2e) in the presence of a catalytic amount of tetrabutylammonium fluoride in THF led to the formation of the corresponding trifluoromethylated silyl ether derivatives 3a– e in almost quantitative yields. Acid hydrolysis of 3a– e gave the desired trifluoromethylated alcohol derivatives ( 4a– e) in excellent isolated yields. Compounds were characterized by IR, NMR ( 1H, 19F, 13C NMR), GCMS, and elemental analysis. Single crystal X-ray structures of 4a and 4b support the proposed products.

Synthesis of 3′-O-(2-cyanoethyl)-2′-deoxythymidine-5′-phosphate as a model compound for evaluation of cyanoethyl cleavage

An essential and challenging task during the development of our sequencing-by-synthesis (SBS) technique is the evaluation of efficient cyanoethyl (CE) cleavage conditions. For this purpose 3′-O-(2-cyanoethyl)-2′-deoxythymidine-5′-phosphate as a model compound as well as a short DNA oligomer bearing the CE function as terminal group were synthesized and used for various deprotection experiments. As it is already known for 2′-O-CE-protected RNA oligonucleotides, the CE function can be cleaved with tetrabutylammonium fluoride (TBAF) in THF. Indeed, by using 3′-O-(2-cyanoethyl)-2′-deoxythymidine-5′-phosphate as a simple model compound for cleavage tests, we found out that the 3′-O-CE function is quantitatively cleaved with 1 M TBAF in THF. However, the CE group is also cleaved by other small bases like hydroxy groups under alkaline conditions. The CE cleavage with TBAF in THF gives the fastest and quantitative removal of the CE group under mild conditions for our sequencing-by-synthesis (SBS) application. The efficient removal of the 3′-CE group is crucial for the proof-of-principle of our SBS approach using dye-labeled 3′-CE-blocked dNTPs, which is currently under investigation. Herein we describe the application of 3′-O-(2-cyanoethyl)-2′-deoxythymidine-5′-phosphate as model compound for the development of reversible terminators for the SBS technique. Furthermore we suggest that nucleoside phosphates bearing any removable 3′-modification might be suitable model compounds for cleavage studies in a heterogeneous environment comparable to an oligonucleotide/ aprotic solvent system.

Solid-Phase Synthesis of 2-Amino-2-thiazolines by the Cyclization of N-(2-Hydroxyethyl)thioureas Using TFA

The 2-amono-2-thiazolines have recently gained significant interest as a scaffold that is applicable to the development of bioactive compounds such as pronounced antidepressant agents, potent human nitric oxide synthase inhibitors, octopaminergic-agonists, anthelmintics, and anti-inflammatory agents. The solid phase synthesis of small heterocycles have been considerably studied because it can be applied to the rapid generation of diverse libraries of drug-like compounds. Although there are many wellestablished reports on the solution phase synthesis of 2amino-2-thiazolines scaffolds because of their valuable pharmaceutical properties, very recently we first reported a solid phase synthetic method of 2-amino-2-thiazolines from the cyclization of N-(2-hydroxyethyl)thioureas using dicyclohexylcarbodiimide (DCC). The ring closure of N-(2hydroxyethyl)thioureas can furnish different products depending on the reaction conditions and substrates such as S-cyclized, N-cyclized, or O-cyclized products. Resinbound substrates 6 were designed as precursors to generate 2-amino-2-thiazolines by the S-cyclization, which were conveniently prepared from various commercially available aminoalcohols and isothiocyanates (Scheme 1). We wish to report an alternative and more effective way into the solid phase synthesis of 2-amino-2-thiazolines, using the cyclization of N-(2-hydroxyethyl)thioureas. Scheme 2 shows the synthetic route of the 2-amino-2thiazoline scaffold. The first step in solid phase reactions was the coupling of amino alcohol onto an ArgoGel-MBCHO resin via reductive amination, followed by the protection of the free alcohol 3 with tert-butyldimethylsilyl chloride (TBSCl) according to the previous procedures. Treatment of this intermediate with isothiocyanates afforded the thioureas resin 5, and subsequent deprotection of the silylated hydroxy group with tetrabutyl ammonium fluoride in THF yielded resin 6. The intramolecular cyclization of resin 6 using dicyclohexylcarbodiimide (DCC) gave mainly the required S-cyclized 2-amino-2-thiazolines resin 7 as reported. Then we turned to release the N-(2-hydroxyethyl)thioureas from the resin 6, key intermediate in Scheme 2, by the trifluoroacetic acid (TFA) cleavage to determine the loading capacity of the both amino alcohols and isothiocyanates. The desired thiourea was not obtained but the final product 2-amino-2-thiazoline was released in high yield and purity. This is that the cyclization and cleavage reaction in TFA simultaneously occurred at the same step, thereby saving one step procedure. The results using TFA for the cyclization and cleavage are summarized in Table 1. Resin 6 derived from either aliphatic (entry 7a-b) or aryl isothiocyanates (entry 7c-7k) furnished the required Salkylation products, but aminoalcohol was limited to the primary alcohol. In summary, a solid phase synthetic method was developed for the parallel synthesis of 2-amino-2-thiazolines, using the cyclization of N-(2-hydroxyethyl)thioureas and cleavage in TFA. This synthetic methodology is ideally suited for the automated applications, because all the reactions were carried out under ambient conditions.

Oligoribonucleotide synthesis by the use of 1-(2-cyanoethoxy)ethyl (CEE) as a 2′-hydroxy protecting group

A novel method for the synthesis of oligoribonucleotides using 1-(2-cyanoethoxy)ethyl (CEE) as a 2′-hydroxy protecting group has been developed. A CEE group was introduced to the 2′-position of N-acyl-3′,5′- O-silyl-protected ribonucleosides under acidic conditions in good yields. The 2′- O-CEE group was found to be stable in an aqueous or ethanolic ammonia and was quickly removed by treatment with anhydrous tetrabutylammonium fluoride (TBAF). A combination of the use of N-acyl and 2′- O-CEE protecting groups enabled a reliable and complete two-step deprotection, first with NH 3–EtOH, then with TBAF in THF, without cleavage of internucleotidic linkages.

Studies on Reactions of Thioketones with Trimethyl(trifluoromethyl)silane Catalyzed by Fluoride Ions

Treatment of 2,2,4,4-tetramethylcyclobutane-1,3-dione (6) in THF with CF3SiMe3 in the presence of tetrabutylammonium fluoride (TBAF) yielded the corresponding 3-(trifluoromethyl)-3-[(trimethylsilyl)oxy]cyclobutanone 7 (Scheme 1) via nucleophilic addition of a CF anion at the CO group and subsequent silylation of the alcoholate. Under similar conditions, the ‘monothione' 1 reacted to give thietane derivative 8 (Scheme 2), whereas in the case of ‘dithione' 2 only the dispirodithietane 9, the dimer of 2, was formed (Scheme 3). A conceivable mechanism for the formation of 8 is the ring opening of the primarily formed CF3 adduct A followed by ring closure via the S-atom (Scheme 2). In the case of thiobenzophenones 4, complex mixtures of products were obtained including diarylmethyl trifluoromethyl sulfide 10 and 1,1-diaryl-2,2-difluoroethene 11 (Scheme 4). Obviously, competing thiophilic and carbophilic addition of the CF anion took place. The reaction with 9H-fluorene-9-thione (5) yielded only 9,9′-bifluorenylidene (14; Scheme 6); this product was also formed when 5 was treated with TBAF alone. Treatment of 4a with TBAF in THF gave dibenzhydryl disulfide (15; Scheme 7), whereas, under similar conditions, 1 yielded the 3-oxopentanedithioate 17 (Scheme 9). The reaction of dithione 2 with TBAF led to the isomeric dithiolactone 16 (Scheme 8), and 3 was transformed into 1,2,4-trithiolane 18 (Scheme 10).

Electronic effects and the stereochemistries in rearrangement-displacement reactions of triaryl(halomethyl)silanes with fluoride and with alkoxide ions.

Tetrabutylammonium fluoride (TBAF) reacts with (halomethyl)diphenyl(para-substituted-phenyl)silanes (13, X = Cl), 14 (X = Br), and 15 (X = I) in ether solvents to give fluorodiphenyl(para-substituted-phenylmethyl)silanes (17a) and fluorophenyl(phenylmethyl)(para-substituted-phenyl)silanes (20a) by attack on silicon and migrations of the phenyl or the para-substituted-phenyl groups to C-1 with displacement of chloride ion. Sodium methoxide in dioxane effects rearrangement-displacements of 14 (X = Br) to yield methoxydiphenyl(para-substituted-phenylmethyl)silanes (17b) and methoxyphenyl(phenylmethyl)(para-substituted-phenyl)silanes (20b). The migratory aptitudes of the varied phenyl groups in rearrangement-displacements of 13 with F(-) at 25 degrees C are p-CF(3)-Ph, 2.72 > p-Cl-Ph, 1.67 > Ph, 1.00 > p-CH(3)-Ph, 0.91 > p-CH(3)O-Ph, 0.58 > p-(CH(3))(2)N-Ph, 0.55. For reactions of 14 with sodium methoxide in dioxane, the migratory aptitudes at 23 degrees C are p-CF(3)-Ph, 2.53 > p-Cl-Ph, 1.64 > Ph, 1.00 > p-CH(3)O-Ph, 0.84 > p-CH(5)-Ph, 0.79 > p-(CH(3))(2)N-Ph, 0.68. The migratory aptitudes in the above rearrangement-displacements are increased by electron-withdrawing substituents, and logarithms of the migratory aptitudes give satisfactory linear correlations with sigma and/or sigma-zero values of the phenyl substituents. Hammett correlations however of the migratory aptitudes from reactions of F(-) with 13 (X = Cl) at 0 and -20 degrees C, 14 (X = Br) at 23, 0, and -20 degrees C, and 15 (X = I) at 23 degrees C are not linear. (+)-(Bromomethyl)methyl-1-naphthylphenylsilane (23, +8.29 degrees, cyclohexane) reacts with CsF and with TBAF in THF to give benzylfluoromethyl-1-naphthylsilane (51, = 0.00 degrees, cyclohexane) and fluoromethyl-(1-naphthylmethyl)phenylsilane (52, impure) in 10.4:1 ratio along with unchanged 23 ( 8.29 degrees, cyclohexane). Sodium methoxide and (+)-23 in dioxane at 25 degrees C and at 0 degrees C yield (+)-benzylmethoxymethyl-1-naphthylsilane (64) and (+)-methoxymethyl(1-naphthylmethyl)phenylsilane (65) in approximately 9:1 ratio. The conversions of (+)-23 to (+)-64 occur with >93% inversion about silicon. Reaction of (+)-23 with sodium methoxide at 25 degrees C to give (+)-65 also occurs with inversion. Further, sodium ethoxide and sodium 2-propoxide react with (+)-23 at 20-25 degrees C by rearrangement-displacements on silicon with phenyl migrations to yield (+)-benzylethoxymethyl-1-naphthylsilane (69) and (+)-benzylmethyl-1-naphthyl-2-propoxysilane (70), respectively, each with >95% inversion about silicon. The mechanisms of rearrangement-displacements of 13-15 and (+)-23 by fluoride and by alkoxide ions are discussed.

Synthesis of 3,5-disubstituted-1,2,4-oxadiazoles using tetrabutylammonium fluoride as a mild and efficient catalyst

Tetrabutylammonium fluoride (TBAF) was found to be a mild and efficient catalyst for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles. Using 0.1–1.0 equivalents of TBAF in THF for 1–24 h at room temperature, alkanoyl- and aroyloxyamidines were converted in high yield to the corresponding 3,5-disubstituted-1,2,4-oxadiazoles. A variety of R and R′ substituents were investigated.

Regioselective Introduction of Electrophiles in the 4-Position of 1-Hydroxypyrazole via Bromine-Lithium Exchange.

Two protocols for introduction of electrophiles at the 4-position of 1-hydroxypyrazoles have been developed. The first is deprotonation of 4-bromo-1-[(tert-butyldiphenylsilyl)oxy]pyrazole (6) with LDA to produce the 5-lithio derivative in which the silyl group migrates spontaneously from oxygen to C-5 affording 4-bromo-5-(tert-butyldiphenylsilyl)-1-lithoxypyrazole (8). Subsequent treatment with t-BuLi causes bromine-lithium exchange to give 5-tert-butyldiphenylsilyl-4-lithio-1-lithoxypyrazole which is trapped with electrophiles affording 4-substituted 5-(tert-butyldiphenylsilyl)-1-hydroxypyrazoles 9a-e in a one-pot sequence. The second is treatment of 4-bromo-1-hydroxypyrazole (5) with excess LDA and trimethylsilyl chloride to produce 3,5-bis(trimethylsilyl)-4-bromo-1-hydroxypyrazole (12), which upon sequential metalation with n-BuLi and reaction with electrophiles affords 4-substituted 3,5-bis(trimethylsilyl)-1-hydroxypyrazoles 13a-e. The tert-butyldiphenylsilyl group of 9a and the trimethylsilyl groups of 12 can be removed selectively by treatment with tetrabutylammonium fluoride in THF in the presence of trifluoroacetic acid.

High pressure nucleophilic fluoride-ion substitution reactions: formation of fluoroalkylbenzenes

A series of 1-phenyl-2-tosyloxy- and 1-phenyl-3-tosyloxyalkanes was synthesized and then subjected to tetrabutylammonium fluoride in THF under 15 kbar (1.5 GPa), 8 kbar or 1 bar pressures. The resultant substitution and elimination reaction product distributions were analyzed. The application of pressure enhanced the progress of the fluoride-ion substitution reactions. The degree of selectivity of the one reaction over the other was found to be a function of tosylate substrate structure and the amount of pressure applied. The exclusive formation of fluoroalkanes from 1-phenyl-2-tosyloxyalkane substrates under 15 kbar pressure demonstrated the potential of the pressure method for prospective use in fluorine-18 radiolabelling applications.

Cleavage of Co-C Bond in a Cobaltathiirane by Hydrogen Chloride and Reformation of Co-C Bond by Tetrabutylammonium Fluoride

Abstract The cobaltadithiolene complex, (η5-cyclopentadienyl)(1-methoxycarbonyl-1,2-ethenedithiolato)cobalt(III) (1a) reacts with trimethylsilyldiazomethane by formal addition of Me3SiCH to the Co-S bond to afford a cobaltathiirane (2a). Addition of hydrogen chloride to 2a causes the cleavage of the Co-C bond to give chloro(η5-cyclopentadienyl)[[1-(trimethylsilyl)methylthio-κS]-1-methoxycarbonylethene-2-thiolato-κS]cobalt(III)(4a). By the reaction with tetrabutylammonium fluoride in THF, 4a undergoes loss of Cl and Me3Si to afford (η5-cyclopentadienyl)[(methylene-κC-thio-κS)-1-methoxycarbonylethene-2-thiolato-κS]cobalt(III)(2c).

Selective synthesis of racemic 1- 11C-labelled norepinephrine, octopamine, norphenylephrine and phenylethanolamine using [ 11C]nitromethane

A new and simple method for the selective condensation of no-carrier-added [ 11C]nitromethane ( 1) with various substituted (protected) benzaldehydes to [ β− 11Cβ-nitrophenethyl alcohols was developed. This method which utilizes tetrabutylammonium fluoride in THF as a catalyst gave a condensation yield of 80–90% and a selectivity of 80–90% for [ 11C]nitroalcohol vs [ 11C]nitrostyrene formation within 2 min. Reduction of these [ 11C]nitroalcohols with Raney nickel in formic acid gave the corresponding [ 11C]aminoalcohols in a yield of 60–90%. Boron tribromide was used for the cleavage of 4-methoxy and 3,4-(methylenedioxy) phenol protecting groups. After HPLC-purification, racemic 1- 11C-labelled norepinephrine ( 7), phenylethanolamine ( 4), norphenylephrine ( 5) and octopamine ( 6) were prepared in a 12–30% decay corrected total radiochemical yield (20–50% counted from 1) with an overall synthesis time of 40–70 min from end of bombardment (EOB). The radiochemical purity was >98% and the specific radioactivity 700–1500 Ci/mmol (26–56 GBq/μmol).